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Rabbit hepatitis E virus (HEV3‐ra) is widely distributed in rabbits worldwide and several recent reports found that HEV3‐ra can infect humans. Therefore, people exposed to rabbits are at high risk of HEV infection. This study was conducted to investigate the characteristics and outcomes of HEV3‐ra natural infection in rabbits. Seventy farmed rabbits (3‐month‐old) were surveyed in a farm in Beijing, China. Rabbits tested positive for HEV RNA were followed weekly for testing of HEV RNA, antigen, antibody and alanine aminotransferase (ALT) level. Liver and kidney tissue was collected for histopathology. Complete genome sequencing of the isolated HEV3‐ra strain was performed (CHN‐BJ‐r4, GenBank: MT364355). The infectivity of CHN‐BJ‐r4 was tested in ten naïve rabbits by intravenous injection or gavage. Anti‐HEV antibody and HEV RNA were tested positive in 7.14% (5/70) and 11.4% (8/70) of rabbits, respectively. Eight naturally infected rabbits were followed, and 37.5% (3/8) of the observed rabbits were found to have fecal shedding of HEV ranging from 3‐22 weeks with high viral load (105‐107 copies/g). Two out of eight rabbits showed temporary viremia. Naturally infected rabbits presented elevated ALT level, seroconversion, and liver histopathology. Complete genome of HEV3‐ra isolated in this study shared 84.61%‐94.36% nucleotide identity with known HEV3‐ra complete genomes. The isolated HEV3‐ra strain was infectious and could infect other rabbits through intravenous and fecal–oral route. Naturally infected rabbits showed up to 22‐week fecal virus shedding with high viral load. These features increased the risk of rabbit‐to‐rabbit and rabbit‐to‐human transmission. [ABSTRACT FROM AUTHOR]

Introduction: Laboratory animals are widely used in biomedical research. Surveillance of naturally occurring virus in laboratory animals is important to fully understand the results of animal experiment, control laboratory-acquired infections among research personnel and manage viral transmission within laboratory animal populations. This study aimed to investigate the prevalence of multiple RNA viruses in laboratory animals commonly used in China., Methods: We screened viral RNA for five different potentially zoonotic RNA viruses (astrovirus, coronavirus, hepevirus, hepatovirus and picornavirus) that can be transmitted via the faecal-oral route in 759 faecal samples collected from nine commonly used laboratory animals (mice, rats, monkeys, rabbits, pigs, dogs, ferrets, goats and tree shrews) in China. Viral RNA was screened by broad-spectrum reverse transcription polymerase chain reaction (RT-PCR) using primers annealing in genome-conserved regions. The laboratory mice and rats used in this study were specific-pathogen-free. The other laboratory animals were conventional animals., Results: At least one selected virus was detected in each of the nine sampled laboratory animal types, except tree shrews. The total positive rates of viral RNA for astroviruses, coronaviruses, hepeviruses and picornaviruses in the selected laboratory animals were 4.3%, 7.6%, 8.0% and 1.1%, respectively. Among these, the positivity rates for hepevirus RNA in laboratory ferrets (41.3%) and rabbits (17.8%), astrovirus RNA in laboratory pigs (75.0%) and coronavirus RNA in laboratory ferrets (45.7%) were relatively high. Viral RNA for hepatovirus was negative in all selected laboratory animals. Co-infection with multiple viruses has also been observed in laboratory dogs, pigs, ferrets and rabbits., Conclusions: Our findings highlight the need for the surveillance of natural viral infections in laboratory animals., (© 2025 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Globally, hepatitis E virus (HEV) infections are prevalent. The finding of high viral loads and persistent viral shedding in ejaculate suggests that HEV replicates within the human male genital tract, but its target organ is unknown and appropriate models are lacking. We aimed to determine the HEV tropism in the human testis and its potential influence on male reproductive health. We conducted an ex vivo culture of human testis explants and in vitro culture of primary human Sertoli cells. Clinically derived HEV genotype 1 (HEV1) and HEV3 virions, as well as rat-derived HEV-C1, were used for inoculation. Transcriptomic analysis was performed on testis tissues collected from tacrolimus-treated rabbits with chronic HEV3 infection. Our findings reveal that HEV3, but not HEV1 or HEV-C1, can replicate in human testis explants and primary human Sertoli cells. Tacrolimus treatment significantly enhanced the replication efficiency of HEV3 in testis explants and enabled successful HEV1 infection in Sertoli cells. HEV3 infection disrupted the secretion of several soluble factors and altered the cytokine microenvironment within primary human Sertoli cells. Finally, intratesticular transcriptomic analysis of immunocompromised rabbits with chronic HEV infection indicated downregulation of genes associated with spermatogenesis. HEV can infect the human testicular tissues and Sertoli cells, with increased replication efficiency when exposed to tacrolimus treatment. These findings shed light on how HEV may persist in the ejaculate of patients with chronic hepatitis E and provide valuable ex vivo tools for studying countermeasures.

Infection with hepatitis E virus (HEV) represents a global problem, with over 20 million people infected annually. No specific antiviral drugs are available for treating HEV infection, necessitating the development of novel targeted therapeutics. Here, we report that the N-methyl-D-aspartate receptor (NMDAR) antagonist ifenprodil, a clinically approved drug used to treat idiopathic pulmonary fibrosis (IPF), is an HEV inhibitor in liver-derived cells. In vitro investigation demonstrates that ifenprodil suppresses viral protein expression in a dose-dependent manner in human hepatoma cells by inhibiting early stages of viral infection. We also found that ifenprodil modulates host cell intrinsic biological processes distinct from virus-induced innate immunity, inhibiting HEV RNA accumulation in primary human hepatocytes. Finally, the inhibitory effect of ifenprodil in vivo was also tested in rabbits challenged with the HEV-3ra CHN-BJ-R14 strain. Fecal virus shedding was below the limit of detection in two animals for both ribavirin-treated and ifenprodil-treated rabbits compared to vehicle-treated control animals. Our data demonstrate that ifenprodil is an effective anti-HEV compound with potential as a therapeutic candidate for the treatment of HEV infection., Competing Interests: The authors declare no conflict of interest.

Chronic hepatitis E mostly occurs in organ transplant recipients and can lead to rapid liver fibrosis and cirrhosis. Previous studies found that the development of chronic hepatitis E virus (HEV) infection is linked to the type of immunosuppressant used. Animal models are crucial for the study of pathogenesis of chronic hepatitis E. We previously established a stable chronic HEV infection rabbit model using cyclosporine A (CsA), a calcineurin inhibitor (CNI)-based immunosuppressant. However, the immunosuppression strategy and timing may be optimized, and how different types of immunosuppressants affect the establishment of chronic HEV infection in this model is still unknown. Here, we showed that chronic HEV infection can be established in 100% of rabbits when CsA treatment was started at HEV challenge or even 4 weeks after. Tacrolimus or prednisolone treatment alone also contributed to chronic HEV infection, resulting in 100% and 77.8% chronicity rates, respectively, while mycophenolate mofetil (MMF) only led to a 28.6% chronicity rate. Chronic HEV infection was accompanied with a persistent activation of innate immune response evidenced by transcriptome analysis. The suppressed adaptive immune response evidenced by low expression of genes related to cytotoxicity (like perforin and FasL ) and low anti-HEV seroconversion rates may play important roles in causing chronic HEV infection. By analyzing HEV antigen concentrations with different infection outcomes, we also found that HEV antigen levels could indicate chronic HEV infection development. This study optimized the immunosuppression strategies for establishing chronic HEV infection in rabbits and highlighted the potential association between the development of chronic HEV infection and immunosuppressants.IMPORTANCEOrgan transplant recipients are at high risk of chronic hepatitis E and generally receive a CNI-based immunosuppression regimen containing CNI (tacrolimus or CsA), MMF, and/or corticosteroids. Previously, we established stable chronic HEV infection in a rabbit model by using CsA before HEV challenge. In this study, we further optimized the immunosuppression strategies for establishing chronic HEV infection in rabbits. Chronic HEV infection can also be established when CsA treatment was started at the same time or even 4 weeks after HEV challenge, clearly indicating the risk of progression to chronic infection under these circumstances and the necessity of HEV screening for both the recipient and the donor preoperatively. CsA, tacrolimus, or prednisolone instead of MMF significantly contributed to chronic HEV infection. HEV antigen in acute infection phase indicates the development of chronic infection. Our results have important implications for understanding the potential association between chronic HEV infection and immunosuppressants., Competing Interests: The authors declare no conflict of interest.

Background: Gout is a common and debilitating condition that is associated with significant morbidity and mortality. Despite advances in medical treatment, the global burden of gout continues to increase, particularly in high-sociodemographic index (SDI) regions., Objective: To address the aforementioned issue, we used age-period-cohort (APC) modeling to analyze global trends in gout incidence and prevalence from 1990 to 2019., Methods: Data were extracted from the Global Burden of Disease Study 2019 to assess all-age prevalence and age-standardized prevalence rates, as well as years lived with disability rates, for 204 countries and territories. APC effects were also examined in relation to gout prevalence. Future burden prediction was carried out using the Nordpred APC prediction of future incidence cases and the Bayesian APC model., Results: The global gout incidence has increased by 63.44% over the past 2 decades, with a corresponding increase of 51.12% in global years lived with disability. The sex ratio remained consistent at 3:1 (male to female), but the global gout incidence increased in both sexes over time. Notably, the prevalence and incidence of gout were the highest in high-SDI regions (95% uncertainty interval 14.19-20.62), with a growth rate of 94.3%. Gout prevalence increases steadily with age, and the prevalence increases rapidly in high-SDI quantiles for the period effect. Finally, the cohort effect showed that gout prevalence increases steadily, with the risk of morbidity increasing in younger birth cohorts. The prediction model suggests that the gout incidence rate will continue to increase globally., Conclusions: Our study provides important insights into the global burden of gout and highlights the need for effective management and prophylaxis of this condition. The APC model used in our analysis provides a novel approach to understanding the complex trends in gout prevalence and incidence, and our findings can inform the development of targeted interventions to address this growing health issue., (©Qiyu He, Tsz-Ngai Mok, Tat-Hang Sin, Jiaying Yin, Sicun Li, Yiyue Yin, Wai-Kit Ming, Bin Feng. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 07.06.2023.)

Background: Invasive puncture biopsy is currently the main method of identifying benign and malignant pulmonary nodules (PNs). This study aimed to investigate the application effect of chest computed tomography (CT) images, tumor markers (TMs), and metabolomics in the identification of benign and malignant PNs (MPNs)., Methods: A total of 110 patients with PNs who were hospitalized in Dongtai Hospital of Traditional Chinese Medicine from March 2021 to March 2022 were selected as the study cohort. A retrospective analysis study of chest CT imaging, serum TMs testing, and plasma fatty acid (FA) metabolomics was performed on all participants., Results: According to the pathological results, participants were divided into a MPN group (n=72) and a benign PN (BPN) group (n=38). The morphological signs of CT images, the levels and positive rate of serum TMs, and the plasma FA indicator were compared between groups. There were significant differences between the MPN group and the BPN group in the CT morphological signs, including location of PN and the number of patients with or without lobulation sign, spicule sign, and vessel convergence sign (P<0.05). Serum carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA 21-1), neuron-specific enolase (NSE), and squamous cell carcinoma antigen (SCC-Ag) were not significantly different between the 2 groups. The serum contents of CEA and CYFRA 21-1 in the MPN group were remarkably higher than those in the BPN group (P<0.05). The plasma levels of palmitic acid, total omega-3 polyunsaturated FA (W3), nervonic acid, stearic acid, docosatetraenoic acid, linolenic acid, eicosapentaenoic acid, total saturated FA, and total FA were much higher in the MPN group than the BPN group (P<0.05)., Conclusions: In conclusion, chest CT images and TMs, combined with metabolomics, has a good application effect in the diagnosis of BPNs and MPNs, and is worthy of further promotion., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-250/coif). The authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Due to the COVID-19 pandemic, the teaching of Biopharmaceutical Engineering course was carried out online and completed with satisfactory outcomes. In order to improve the efficiency of online teaching, ensure the substantive equivalence between online and offline teaching and achieve effective teaching, this article summarized the exploration and practical experience of online teaching, taking the Biopharmaceutical Engineering course as an example. This includes analysis of learner characteristics, selection of online teaching platform, development of teaching resources, optimization of teaching contents, BOPPPS teaching method-based design of teaching structure, and reflection of effective teaching. This paper is expected to provide a useful reference for online teaching.